A characteristic feature of sle is the presence of autoantibodies against doublestranded dsdna, histones and nucleosomes, and other chromatin components. Autoimmune hepatitis was initially called chronic active hepatitis and lupoid hepatitis, and was seen in the 1960s as being akin to systemic lupus erythematosus sle by reason of shared features indicative of an autoimmune pathogenesis. Pediatric systemic lupus erythematosus american academy. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli cated and challenging disease to diagnose and treat.
Early studies in lupusprone mice revealed that b cells are absolutely essential for disease induction 48 via both autoantibodydependent. Systemic lupus erythematosus sle is a chronic, multisystem, autoimmune disease characterized by periods of increased disease activity caused by inflammation of blood vessels and connective tissue. A diverse array of genetic factors contribute to the. Jan 16, 2020 t cell subsets are critically involved in the development of systemic autoimmunity and organ inflammation in systemic lupus erythematosus sle. The basic pathological features of sle are that of inflammation and blood vessel abnormalities, which include band or occlusive vasculopathy, vasculitis, and. Clinical presentation, pathophysiology, and therapeutic strategies over the course of disease.
Although the term lupus erythematosus was introduced by 19thcentury physicians to describe skin lesions, it took almost 100 years to realize that the disease is systemic and spares no organ. Sle is an autoimmune disease in which environmental triggers in genetically susceptible individuals results in the activation of the innate and adaptive immune response, leading to a loss of tolerance to ubiquitous selfantigens. Progranulin pgrn is an immunomodulatory protein that is upregulated in sle patients. Renal assault during sle is initiated by genes that breach immune. Review pathogenesis of systemic lupus erythematosus. Sle is a prototype type iii hypersensitivity reaction.
Sep 30, 2011 systemic lupus erythematosus sle is a complex disease characterized by the appearance of autoantibodies against nuclear antigens and the involvement of multiple organ systems, including the kidneys. College of rheumatology classification criteria for systemic lupus erythematosus. Systemic lupus erythematosus sle is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. We discuss the role of pathological factors in the development of skin damage in sle. Pathogenesis 20 and clinical features 1 introduction systemic lupus erythematosus sle is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations encompassing almost all organs and tissues. Tnfr1 and ifnifnr play an important role in the skin injury. There is much interest in biomarkers, but diagnostic and. Pdf pathogenesis of systemic lupus erythematosus researchgate. Pathogenesis of human systemic lupus erythematosus cell press. Pathogenesis of human systemic lupus erythematosus. Oct 24, 2012 systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids. Systemic lupus erythematosus sle is a complex disease characterized by the appearance of autoantibodies against nuclear antigens and the involvement of multiple organ systems, including the kidneys.
Importantly, this gd regulatory population decreased in the peripheral blood of systemic lupus erythematosus patients, suggesting a potential mechanism in. Pathogenesis of systemic lupus erythematosus journal of clinical. A variety of immunological defects contribute to sle, including dysregulated innate and adaptive immune response. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated. It may affect virtually any organ or structure of the body, especially the skin, kidneys, joints, heart, gastrointestinal tract, brain, and serous membranes membranous linings of organs, joints, and cavities of the body. We have made remarkable progress in understanding the genetics of sle over the last five years, including five published whole genome association analyses.
A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved sle. Etiology and pathogenesis of systemic lupus erythematosus. More than 90% of cases of sle occur in women, frequently starting at childbearing age. Crow key points systemic lupus erythematosus sle results from chronic and recurrent activation of the immune system, with production of antibodies and other protein products contributing to inflammation and tissue damage. Systemic lupus erythematosus an overview sciencedirect topics. Inflammation caused by lupus can affect many different body systems including your joints, skin, kidneys, blood cells, brain, heart and lungs. However, research using various mouse strains of spontaneous and inducible. The condition is much more than a positive antinuclear antibody ana. Systemic lupus erythematosus larissa lisnevskaia, grainne murphy, david isenberg systemic lupus erythematosus is a remarkable and challenging disorder. Systemic lupus erythematosus is a complex multisystem autoimmune disorder with a heterogeneous presentation and clinical course. Systemic lupus erythematosus is the most common form of the disease.
Systemic lupus erythematosus sle is a systemic autoimmune disease that predominantly affects the females female to male ratio is 9. Pathogenesis of systemic lupus erythematosus c c mok, c s lau j clin pathol2003. The disease has a waxing and waning course and carries significant morbidity and mortality from some of its complications. Our objective was to update the eular recommendations for the management of systemic lupus erythematosus sle, based on emerging new evidence. Immunologic abnormalities, genetic factors, viruses, and environmental stimuli have been thought to con. Systemic lupus erythematosus sle is a disease characterized by the production of autoreactive antibodies and cytokines, which are thought to have a major. Pathology and pathogenesis of vascular injury in systemic lupus erythematosus interactions of inflammatory cells and activated endothelium h. Systemic lupus erythematosus genetics home reference nih. Moulton,1, abel suarezfueyo,1 esra meidan,1,2 hao li, masayuki mizui,3 and george c. Systemic lupus erythematosis sle is a complex and clinically heterogeneous autoimmune disease.
It can affect the skin, joints, kidneys, brain, and other. Systemic lupus erythematosus sle is a chronic autoimmune disease affecting multiple organs. Systemic lupus erythematosus sle is an autoimmune disease characterized by complex immunological pathogenesis and diverse clinical features, as a consequence of multisystem inflammation. It is more common in african americans and people of american indian and asian descent than in. However, the factors involved in regulating the pathogenesis of sle by pgrn are largely unknown. The common manifestations are in the form of arthritis, skin rash, renal and hematological involvement along with fever and constitutional symptoms. Multiple genes contribute to disease susceptibility. Immune system exposure to excessive amounts of autoantigens that are not efficiently removed is reported to play a significant role in the generation of autoantibodies and the pathogenesis of sle. Tcell signaling alteration in systemic lupus erythematosus sle.
Most people suffering from systemic lupus erythematosus will develop pain in their muscles, joints and peripheral joints such as joints in their hands and knees can often become inflamed. The interaction of sex, hormonal milieu, and the hypothalamopituitaryadrenal axis modifies this susceptibility and the clinical. Symptoms vary between people and may be mild to severe. Its diversity of clinical features is matched by the complexity of the factors genetic, hormonal, and environmental that cause it, and the array of autoantibodies with which it is associated. Aug 15, 2016 systemic lupus erythematosus, the most common form of lupus, is a chronic autoimmune disease that can cause severe fatigue and joint pain. Immunological pathogenesis and treatment of systemic lupus. Although both men and women of all age groups can be affected, women outnumber men almost 10 fold and. Pathogenesis of skin injury of systemic lupus erythematosus. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli. Disease severity is wide ranging, with most suffering milder. Mar 31, 2015 systemic lupus erythematosus sle is a complex, autoimmune disorder that can have debilitating effects on various organs, including the kidneys. Systemic lupus erythematosus sle, lupus is characterized by a.
Systemic lupus erythematosus sle is an autoimmune disease. A candidate source of autoantigen is the neutrophil extracellular trap net, which releases nucleic acids into the extracellular environment, generating a structure composed of dna coated with. A plasmacytoid dendritic cellstype i interferon axis is critically implicated in the pathogenesis of systemic lupus erythematosus. Systemic lupus erythematosus sle is a chronic autoimmune disease with a broad spectrum of clinical presentations and manifestations that can affect virtually any organ or tissue of the body. The role of microparticles in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Systemic lupus erythematosus sle is an autoimmune disease caused by the disorders of immune regulation but its pathogenesis is poorly understood. Lupus is a systemic autoimmune disease that occurs when your bodys immune system attacks your own tissues and organs. Pdf the exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Sunlightinduced pathogenesis in systemic lupus erythematosus systemic lupus erythematosus sle is an extremely heter ogen eous disorder which produces a broad spectrum of ill ness in patients. Apr 12, 2020 in systemic lupus erythematosus sle, many geneticsusceptibility factors, environmental triggers, antigenantibody ab responses, bcell and tcell interactions, and immune clearance processes. Systemic lupus erythematosus sle is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course. Vyse, in genomic and personalized medicine second edition, 20. Lie systemic lupus erythematosus sle is an auto immune disease characterized by immune dysregula tion that results in the production of autoantibodies.
While systemic lupus can affect any area of the body, most people experience symptoms in only a few organs. The disease has a waxing and waning course and carries significant. Cellular and molecular pathogenesis of systemic lupus. Genetics and pathogenesis of systemic lupus erythematosus. Clinical and laboratory findings in seventeen patients.
There is much interest in biomarkers, but diagnostic and disease activity markers in actual clinical. Systemic lupus erythematosus an overview sciencedirect. Skin deposited igg is a crucial pathologic factor in the development of skin damage in sle. Aberrant innate immune responses play a significant role in the pathogenesis of sle. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably involved. What is the pathogenesis of systemic lupus erythematosus sle. An extremely complicated and multifactorial interaction among. The precise immunological events that trigger the onset of clinical manifestations of sle are not yet well understood. Timely detection of sle is important, because prompt treatment can prevent its many major complicationsnotably, end organ damage. Systemic lupus erythematosus sle, is the most common type of lupus. In this seminar we reflect on changes in its classification criteria. Overview of the pathogenesis of systemic lupus erythematosus.
Apr 25, 2014 systemic lupus erythematosus sle is a systemic autoimmune disease with various clinical manifestations affecting different tissues. Systemic lupus erythematosus sle is a complex, autoimmune disorder that can have debilitating effects on various organs, including the kidneys. It can be life threatening when major organs are involved. Systemic lupus erythematosus has many guises, but the unifying feature is the presence of antibodies against doublestranded dna in almost all patients.
The most common issue for patients suffering from systemic lupus erythematosus is to do with their joints somers et al 2007. Defective immune regulatory mechanisms, such as the clearance of apoptotic cells and immune complexes, are important contributors to the development of sle. It is more common in african americans and people of american indian and asian descent than in white people. In this disease, the immune system of the body mistakenly attacks healthy tissue. Systemic lupus erythematosus sle is a chronic systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. Erythematosus pathogenesis of systemic lupus and their.
The exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Influence of functional interleukin 10tumor necrosis factoralpha polymorphisms on interferonalpha, il10, and regulatory t cell population in patients with systemic lupus. Sunlightinduced pathogenesis in systemic lupus erythematosus. Systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids. What is the pathogenesis of systemic lupus erythematosus. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably. Systemic lupus erythematosus sle is an autoimmune disease caused by cells represented in the peripheral blood circulation 57.
Most people suffering from systemic lupus erythematosus will develop pain in their muscles, joints and peripheral joints such as joints. The second most common clinical expression in lupus patients is skin damage that the pathogenesis remains unclear. Thus, testing of biomarkers against these criteria is an important area for future research. Genetics and pathogenesis of systemic lupus erythematosus and. Interplay of cytokines and chemokines in the pathogenesis of systemic lupus erythematosus.
Progranulin mediates proinflammatory responses in systemic. Systemic lupus erythematosus sle, lupus is characterized by a global loss of selftolerance with activation of autoreactive t and b cells leading to production of pathogenic autoantibodies and tissue injury. The loss of immune tolerance, increased antigenic load, excess t cell help, defective b cell suppression, and the shifting of t helper 1. Nadph oxidase inhibits the pathogenesis of systemic lupus. The source of autoantigen that drives disease onset and progression is unclear. The signs and symptoms of sle vary among affected individuals, and can involve many organs and systems, including the skin, joints, kidneys, lungs, central nervous.
Systemic lupus erythematosus university of louisville. Systemic lupus erythematosus in patients with chronic cutaneous discoid lupus erythematosus. Systemic lupus erythematosus sle is a disease characterized by the production of autoreactive antibodies and cytokines, which are thought to have a major role in disease activity and progression. Sle is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. Systemic lupus erythematosus sle is an immunemediated disease whose originating pathogenesis results in autoantigen exposure giving rise to numerous autoreactive antibodies of varying antigenic specificities that along with a myriad of cytokines are thought to be effectors of disease activity. Innate immune mechanisms are necessary for the aberrant adaptive immune responses in sle. Systemic lupus erythematosus overview the lupus initiative. The pathogenesis of systemic lupus erythematosus an update. Lupus, technically known as systemic lupus erythematosus sle, is an autoimmune disease in which the bodys immune system mistakenly attacks healthy tissue in many parts of the body. Systemic lupus erythematosus is a systemic autoimmune disease with a worldwide distribution.
Although accreditation for this cecme activity has expired, and the posttest is no longer available, you can still read the full article. Systemic lupus erythematosus lupus is a chronic longlasting autoimmune disease that can affect many parts of the body. Introduction systemic lupus erythematosus sle is a chronic autoimmune disease of unknown cause that can affect virtually any organ of the body. Breakdown of selftolerance is the main pathogenesis of sle. Immunologic abnormalities, especially the production of a number of antinuclear antibodies ana, are a prominent feature of the disease. Pathogenesis of systemic lupus erythematosus journal of. A complex interaction of genetics, environment, and hormones. Systemic lupus erythematosus is a remarkable and challenging disorder.
Systemic lupus erythematosus sle etiology likely involves complex interactions between genetic and environmental stimuli that lead to autoantibody production and chronic inflammation. Expires july 31, 2017 systemic lupus erythematosus sle is a chronic autoimmune disease that often goes undiagnosed initially. Approximately 4070% of patients with sle will develop lupus nephritis. The pathogenesis is multifactorial with evidence of genetic susceptibility, environmental triggers, and aberrancy in both the innate and adaptive immune systems. Infections in early systemic lupus erythematosus pathogenesis.
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